DIAGNOSIS AND TREATMENT OF CHRONIC HEPATITIS C INFECTION ( by Dena Nazer, Hisham Nazer).

Overview

The hepatitis C virus (HCV) is a major public health problem and a leading cause of death from liver disease in the United States. Although generally benign in its acute presentation, in more than 70% of patients, HCV infection tends to become chronic, at which stage it can induce end-stage liver disease and hepatocellular carcinoma. Thorough investigation of chronic hepatitis is of vital importance to discover the cause of liver inflammation, assess its severity, and plan treatment. The diagnosis, staging, and treatment of HCV infection according to the most recent studies and recommendations are discussed here.

Diagnosis of HCV infection

Tests for diagnosis of HCV are divided into serologic and molecular assays.

Serologic assays include the screening tests for antibodies to HCV and supplemental antibody testing. The enzyme immunoassay (EIA) and the enzyme-linked immunosorbent assay (ELISA) are the 2 most commonly used screening tests for HCV antibodies. The positive predictive value of ELISA depends on the patient being tested; it is greater than 95% in patients at high risk for HCV infection and only 50-61% in patients at low risk. Three generations of EIA testing have been developed. In addition to its ease of use, low variability, and relatively low cost, the newer generations of EIA have added HCV antigens in the test, increasing its sensitivity and specificity. In certain patient populations, mostly in immunosuppressed patients and patients on long-term hemodialysis, an expression of antibody to HCV may be lacking. ELISA testing may also fail to detect HCV in 2-5% of patients. Supplemental testing using the recombinant immunoblot assay helps to confirm positive values and may also help to resolve the false-positive EIA results. Molecular assays testing for HCV RNA are replacing the use of supplemental tests.

Molecular assays are divided into qualitative, quantitative, and genotype tests. Qualitative tests sensitively detect the HCV RNA in the patient’s blood serum. It can be detected by polymerase chain reaction (PCR) or by transcription-mediated amplification. Quantitative tests are used for quantifying HCV RNA viral load before, during, and after treatment. Target amplification methods, such as quantitative PCR, and signal amplification technologies, such as branched DNA assay, are used.

Genotype testing is of vital importance in patients with chronic HCV infection. It can be performed by direct sequence analysis, by reverse hybridization to genotype-specific oligonucleotide probes, or by restriction fragment length polymorphisms. HCV has 6 major genotypes. The exact genotype should be determined in all persons infected with HCV prior to treatment in order to determine the duration of therapy and the likelihood of response.

To diagnose HCV infection, the patient is initially screened for antibodies to HCV. In patients with positive antibodies to HCV or potentially false-negative test results, the diagnosis is confirmed with HCV RNA tests. Genotype testing is an important next step to determine the duration of therapy and to predict the response to treatment. A liver biopsy provides the most accurate estimation of the severity of tissue damage and is indicated when results would influence whether treatment is recommended. A biopsy is not mandatory in order to initiate treatment. Tests to detect fibrosis look promising and may also be an alternative to liver biopsy in the future, but they are currently used only for drug trials.